Chromosome stability of synthetic Triticum turgidum-Aegilops umbellulata hybrids.

BACKGROUND: Unreduced gamete formation during meiosis plays a critical role in natural polyploidization. However, the unreduced gamete formation mechanisms in Triticum turgidum-Aegilops umbellulata triploid F1 hybrid crosses and the chromsome numbers and compostions in T. turgidum-Ae. umbellulata F2 still not known. RESULTS: In this study, 11 T.turgidum-Ae. umbellulata triploid F1 hybrid crosses were produced by distant hybridization. All of the triploid F1 hybrids had 21 chromosomes and two basic pathways of meiotic restitution, namely first-division restitution (FDR) and single-division meiosis (SDM). Only FDR was found in six of the 11 crosses, while both FDR and SDM occurred in the remaining five crosses. The chromosome numbers in the 127 selfed F2 seeds from the triploid F1 hybrid plants of 10 crosses (no F2 seeds for STU 16) varied from 35 to 43, and the proportions of euploid and aneuploid F2 plants were 49.61% and 50.39%, respectively. In the aneuploid F2 plants, the frequency of chromosome loss/gain varied among genomes. The chromosome loss of the U genome was the highest (26.77%) among the three genomes, followed by that of the B (22.83%) and A (11.81%) genomes, and the chromosome gain for the A, B, and U genomes was 3.94%, 3.94%, and 1.57%, respectively. Of the 21 chromosomes, 7U (16.54%), 5 A (3.94%), and 1B (9.45%) had the highest loss frequency among the U, A, and B genomes. In addition to chromosome loss, seven chromosomes, namely 1 A, 3 A, 5 A, 6 A, 1B, 1U, and 6U, were gained in the aneuploids. CONCLUSION: In the aneuploid F2 plants, the frequency of chromosome loss/gain varied among genomes, chromsomes, and crosses. In addition to variations in chromosome numbers, three types of chromosome translocations including 3UL·2AS, 6UL·1AL, and 4US·6AL were identified in the F2 plants. Furthermore, polymorphic fluorescence in situ hybridization karyotypes for all the U chromosomes were also identified in the F2 plants when compared with the Ae. umbellulata parents. These results provide useful information for our understanding the naturally occurred T. turgidum-Ae. umbellulata amphidiploids.

Phylogeny and Fungal Community Structures of Helotiales Associated with Sclerotial Disease of Mulberry Fruits in China.

Mulberry fruit sclerotiniose is a prevalent disease caused by the fungal species Ciboria shiraiana, C. carunculoides, and Scleromitrula shiraiana of the order Helotiales, and severely affects the production of mulberry. However, these species have only been identified using morphological and rDNA-ITS sequence analyses, and their genetic variation is unclear. To address this, morphological and two-locus (ITS and RPB2) phylogenetic analyses were conducted using culture-dependent and independent methods for 49 samples from 31 orchards across four provinces in China. Illumina MiSeq sequencing was used to assess the fungal communities obtained from fruits varying in disease severity and color from an orchard in Wuhan. Conidial suspensions of C. shiraiana and C. carunculoides isolated from diseased fruits, diseased fruits affected with hypertrophy and pellet sorosis sclerotiniose, and mycelia of Sclerotinia sclerotiorum were determined to be pathogenic to the mulberry cultivar YSD10. However, fruits inoculated with S. sclerotiorum mycelia exhibited nontypical disease symptoms, and mycelia and conidia obtained from C. carunculoides and S. shiraiana strains were not pathogenic. Maximum parsimony and Bayesian analyses using the sequences of the assessed loci indicated species variability with no evidence of geographic specialization. Metagenomic analysis revealed that the diversity of fungal communities was reduced with disease progression. Furthermore, within a single fruit, the presence of two Ciboria spp. was detected. These results provide novel insights into Ciboria spp., revealing the secondary infections caused by conidia in diseased fruits, genetic variations of the pathogens, and the occurrence of coinfection. This improved understanding of fungal pathogens will aid in developing effective disease control strategies.

Attenuated African swine fever virus through serial passaging of viruses in cell culture: a brief review on the knowledge gathered during 60 years of research.

African swine fever virus (ASFV) is a highly pathogenic double-stranded DNA virus. It affects various breeds of pigs, causing serious economic losses and health threats because of its rapid spread and high pathogenicity and infectivity. This situation is not helped by the lack of a validated vaccine or effective therapies. Since the 1960s, different strains of ASFV have been subjected to serial passage in a variety of cell lines. The attenuated ASFV strains obtained through serial passage are not only candidates for ASF vaccine research, but also are useful to study the molecular genetic characteristics and pathogenic mechanism of the virus. This review summarizes related studies on the attenuated strains of ASFV acquired through cell passage over the last 60 years, with the aim of providing inspiration for the rational design of vaccines in future.

First Report of Neocosmospora mori Causing Root Rot and Stem Blight of Mulberry in Nanzhang, Hubei, China.

Mulberry (Morus alba L.) has been cultivated for thousands of years in many temperate regions in East Asia and is commonly used to feed silkworms. In May 2021, 5 to 8% incidence of stem blight on 4-year-old mulberry 'Nongsang 14' was observed in several orchards in Nanzhang County, Hubei Province, China. The roots and stems showed symptoms of vascular discoloration, and the tender new shoots, surrounded by white hyphae, were detached easily. Symptomatic stem tissues (5 mm × 5 mm) were excised from the border between diseased and healthy tissues, surface sterilized in a 75% ethanol solution for 30 s and 2.5% sodium hypochlorite for 1.5 min, washed three times in sterile distilled water, then placed on potato dextrose agar (PDA, 250 g potatoes, 2% dextrose, 1.6% agar), and incubated at 25°C in darkness. Two isolates (Bq2 and Bq3) were subcultured using the single-spore method. On PDA, colonies were cottony, with whitish aerial mycelium and the daily growth rate was 4.25 to 5.50 mm/day at 25°C in darkness. On carnation leaf agar, macroconidia were fusiform with slightly curved apical cells and foot-shaped basal cells, three to five septate, measuring 47.5 to 80.3 × 3.6 to 5.6 µm (average 68.7 × 4.7 µm, n = 30). On spezieller nährstoffarmer agar, microconidia were produced in false heads on monophialides, mostly 0-septate, oval, obovoid, or reniform in shape, measuring 5.1 to 10.7 × 2.7 to 5.3 µm (average 8.5 × 3.3 µm, n = 30). Chlamydospores were 4.9 to 11.0 µm in diameter (average 6.8 µm, n = 30), round shaped, thick-walled, and produced individually or in pairs or in chains. For molecular identification, the ribosomal internal transcribed spacers (ITS), translation elongation factor 1α (EF-1α), 28S large subunit nrDNA (LSU), and calmodulin (CAM) genes were amplified and sequenced with primers ITS1/ITS4 (White et al. 1990), EF1H/EF2T (O'Donnell et al. 1998), LR0R/LR5 ( Vilgalys and Hester 1990; Vilgalys and Sun 1994), and CL1/CL2A (Geiser et al. 2021; Wang et al. 2011), respectively. The sequences were deposited in GenBank (OQ711943-OQ711944 for ITS, OQ722438- Q722439 for EF-1α, OQ722441-OQ722442 for CAM, and OR116152-OR116153 for LSU). A maximum-likelihood phylogenetic analysis based on multilocus sequences was conducted using MEGA7, which showed that the two isolates grouped into a clade with Neocosmospora mori (previously Fusarium solani species complex) supported by a high bootstrap value (85%), and hence, they were identified as N. mori based on morphological and molecular analyses (Brooks et al. 2022; Crous et al. 2021; Lombard et al. 2015; Zeng and Zhuang 2023). To complete Koch's postulates, three healthy 2-month-old seedlings grown in sterile peat mix were removed from pots and the roots were washed in sterile water. Each plant was inoculated by dipping wounded and unwounded roots in a spore suspension (1 × 107 conidia/ml) for 20 min, and then 10 mL of the spore suspension was poured over the roots of each seedling after transplanting. Three plants were treated with sterilized water as a control. The tested plants were then kept in a plastic box containing sterile water and incubated at 25°C in a 12 h/12 h light/dark cycle. The pathogenicity assay was repeated three times for each isolate. Root and stem blight was observed 10 days after inoculation, while the control plants were asymptomatic. Furthermore, fungi with morphological characteristics of N. mori were only reisolated from the symptomatic stems and sequences of LSU matched those of isolates Bq2 and Bq3. This pathogen has been reported previously causing stem blight on mulberry trees in Japan and South Korea (Sandoval-Denis et al. 2019), but to our knowledge, this is the first report of N. mori causing root rot and stem blight of mulberry in China. This report will facilitate the development of effective control strategies for the disease.

First Report of Colletotrichum aenigma Causing Anthracnose on Mulberry Leaves in China.

Mulberry (Morus alba L.) has been grown worldwide as a crop for silkworm rearing for over five thousand years (Jiao et al. 2020). In July 2021, a leaf spot disease was observed on mulberry leaves in Wuhan city (114°33'E, 30°48'N), Hubei province, China, with approximately 40% of leaves (about 300 trees) affected. Early symptoms were light brown, with small lesions subsequently expanding to larger sometimes irregular dark brown or black spots surrounded by yellow-brown margins, with easily perforated necrotic lesions. Leaf tissues (5 mm×5 mm) were excised from the border between diseased and healthy tissues, surface sterilized with 75% ethanol solution for 30 s and 2.5% sodium hypochlorite for 2 min, washed thrice in sterile distilled water, and then placed on potato dextrose agar (PDA), and incubated at 25°C in darkness. Four isolates (C1, C9, CHS2, and CHS6) were subcultured using the single-spore method. On PDA, colonies were cottony, pale white from above, and white to grayish-green on the reverse side. Conidia were aseptate, hyaline, subcylindrical with broadly rounded ends, 8.4 to 18.3×4.1 to 7.7 µm (mean = 13.9×5.5 µm, n = 30). Appressoria were typically elliptic or irregular with a few lobes, dark brown, 5.9 to 9.6×4.2 to 8.1 µm (mean = 7.9 ×5.7 µm, n = 30). The morphological characteristics of the isolates matched the descriptions of Colletotrichum gloeosporioides species complex (Weir et al. 2012). The isolates were further identified by analysis of the ribosomal internal transcribed spacers (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), calmodulin (CAL), actin (ACT), chitin synthase (CHS-1), glutamine synthetase (GS), and ß-tubulin 2 (TUB2) genes, amplified respectively with ITS1/ITS4, GDF/GDR, CL1C/CL2C, ACT-512F/ACT-783R, CHS-79F/CHS-345R, GSF1/GSR, and Bt2a/Bt2b (Glass and Donaldson 1995; Weir et al. 2012; White et al. 1990). The sequences were deposited in GenBank (ON492187-ON492214). Concatenated sequences of the seven genes in addition to Colletotrichum species sequences from GenBank were used to conduct a phylogenetic analysis using Maximum-Likelihood (ML) method in MEGA7. The four isolates were grouped into a clade with Colletotrichum aenigma supported by a high bootstrap value (89%), and hence, they were identified as C. aenigma based on the morphological and molecular analyses. To confirm Koch's postulates, wounded leaves of six healthy 2-month-old seedlings made by a sterile needle were inoculated with each isolate by spraying 10 ml of conidial suspensions (105 conidia/ml) on each plant, and the control plants were treated with sterile distilled water. All the treated plants were kept in a plastic box containing sterile water and incubated at 28°C in a 12 h/12 h light/dark cycle. The test was performed three times. After 7 days, typical anthracnose lesions appeared on all inoculated leaves, whereas control plants remained asymptotic. Furthermore, C. aenigma was only reisolated from the symptomatic leaves. Previous studies reported five Colletotrichum species (C. morifolium, C. fioriniae, C. brevisporum, C. karstii, and C. kahawae subsp. ciggaro) to cause this disease on mulberry in China (Tian, 1981; Xue et al. 2019). To our knowledge, this is the first report of C. aenigma causing anthracnose on mulberry in China. The finding will facilitate epidemiological studies and the development of effective control strategies for the disease.

Identification and Characterization of Wheat-Aegilops comosa 7M (7A) Disomic Substitution Lines with Stripe Rust and Powdery Mildew Resistance.

Aegilops comosa (MM, 2n = 2x = 14), an important diploid species from the wheat tertiary gene pool, contains many unique genes/traits of potential use for wheat breeding, such as disease resistance. In this study, three sister lines, NAL-32, NAL-33, and NAL-34, were identified from a wheat-A. comosa distant cross using fluorescence in situ hybridization, simple sequence repeat markers, and PCR-based unique gene markers combined with single nucleotide polymorphism (SNP) array analysis. Genetically, NAL-32 contained neither an alien nor translocation chromosome, whereas NAL-33 and NAL-34 had disomic 7M (7A) substitution chromosomes but differed in the absence or presence of the 1BL/1RS translocation chromosomes, respectively. The absence of 7A in NAL-33 and NAL-34 and the unusual 1B in the latter were verified by wheat 55K SNP arrays. The two 7M (7A) substitution lines had similar levels of resistance to stripe rust and powdery mildew, but better than that of NAL-32 and their common wheat parents, suggesting that the stripe rust and powdery mildew resistance of NAL-33 and NAL-34 were derived from the 7M of A. comosa. This research provides important bridge materials that can potentially be used for transferring stripe rust and powdery mildew resistance.

Phenolic profiles, antioxidant activity and inhibition of digestive enzymes of water caltrop pericarps.

BACKGROUND: Water caltrop (Trapa natans L.) is widely cultivated as a popular vegetable or fruit in Asian countries. In China, water caltrop pericarp is also used as a functional food to treat metabolic syndrome. However, the profiling of bioactive substances and their pharmacological activities in different water caltrop varieties remains to be investigated. In the present study, three varieties of water caltrop pericarps collected from 13 origins in China were analyzed for their phenolic substances. To investigate the pharmacological activities, samples were tested for their free radical scavenging capacity and inhibitory potency against α-glucosidase and pancreatic lipase. RESULTS: In total, 46 phenolic compounds were identified in the ethanol extract of water caltrop pericarp using a liquid chromatography-quadrupole time of flight-tandem mass spectrometry method, most of which were hydrolyzable tannins. Two cultivated varieties samples exhibited a relatively higher phenolic content and stronger antioxidant and inhibitory activities against α-glucosidase and pancreatic lipase compared to those from the wild variety. Correlation analysis between phenolic contents and biological activities suggested that phenolic compounds exhibited potential free radical scavenging capacity, α-glucosidase and pancreatic lipase inhibitory activities. CONCLUSION: It is concluded that the phenolic compounds of water caltrop pericarp are promising sources of natural antioxidants, α-glucosidase and pancreatic lipase inhibitors. © 2021 Society of Chemical Industry.

Self-Assembling Nanoparticle Vaccines Displaying the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Responses in Rhesus Monkeys.

SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 µg of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross-neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 × 105 CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates.

Production and characterization of a disomic 1M/1D Triticum aestivum-Aegilops comosa substitution line.

PI 554419, formerly designated as Ae. uniaristata, showed significant difference with other Ae. uniaristata and Ae. comosa accessions in morphological traits at the seedling stage and its leaf color, length, and width behaved as an intermediate type. In this study, we reclassified PI 554419 as Ae. comosa subsp. comosa by comparing the fluorescence in situ hybridization (FISH) signals and the patterns of PCR-based landmark unique gene (PLUG) markers and conserved orthologous set (COS) markers of PI 554419 with other Ae. uniaristata and Ae. comosa accessions as well as the taxonomic character of spike morphology. A disomic 1M/1D substitution line NB 4-8-5-9 derived from PI 554419 was identified from a distant hybridization of Ae. comosa with common wheat (STM 10/CSph1b//CM 39///13 P2-6) by the molecular cytological method. Furthermore, the agronomic and seed morphological traits, as well as the flour processing quality properties of NB 4-8-5-9, were compared with those of its three common wheat parents in two different locations during the 2017-2018 growing seasons. The agronomical traits of NB 4-8-5-9 were similar to or even better than its parents. The seed size-related traits of NB 4-8-5-9 were better than those of all three parents, and the 1000-grain weight and grain width were close to those of Chuanmai 39 (CM 39) and 13 P2-6 and larger than those of CSph1b. The processing quality properties of NB 4-8-5-9 were more similar to those of 13 P2-6 and CSph1b but less similar to those of CM 39. The 1M/1D substitution line NB 4-8-5-9 could further be used for developing translocation lines with 1M segment. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01207-2.

Stability of pure oxygen aeration-activated sludge system under non-steady food-to-microorganism ratio conditions during petrochemical wastewater treatment.

This study investigates the stability of a pure oxygen aeration-activated sludge system for petrochemical wastewater treatment under high organic concentration and non-steady food-to-microorganism (F/M) ratio conditions. Sludge settling characteristics maintained relatively stable conditions with an F/M ratio variation from 0.15 ± 0.04 to 0.33 ± 0.07 kg COD/kg MLSS⋅d, while the excess F/M ratio (0.44 ± 0.16 kg COD/kg MLSS⋅d) resulted in deterioration of the organic removal and sludge-water separation performances. Loosely bound extracellular polymeric substances (EPS) showed more significant effect on sludge settleability than the tightly bound EPS. The genus Hydrogenophaga was related to organic removal performance, while Zoogloea and Chitinophaga were related to the effluent quality of suspended solids. The excess F/M ratio also caused an increase in Zoogloea and Chitinophaga, whereas the toxicity of petrochemical wastewater resulted in decreased abundance of Hydrogenophaga. These changes caused deterioration of the organic removal and sludge-water separation performances.

Development and characterization of Triticum turgidum - Aegilops comosa and T. turgidum - Ae. markgrafii amphidiploids.

Aegilops comosa and Ae. markgrafii are diploid progenitors of polyploidy species of Aegilops sharing M and C genomes, respectively. Transferring valuable genes/traits from Aegilops into wheat is an alternative strategy for wheat genetic improvement. The amphidiploids between diploid species of Aegilops and tetraploid wheat can act as bridges to overcome obstacles from direct hybridization and can be developed by the union of unreduced gametes. In this study, we developed seven Triticum turgidum - Ae. comosa and two T. turgidum - Ae. markgrafii amphidiploids. The unreduced gametes mechanisms, including first-division restitution (FDR) and single-division meiosis (SDM), were observed in triploid F1 hybrids of T. turgidum - Ae. comosa (STM) and T. turgidum - Ae. markgrafii (STC). Only FDR was observed in STC hybrids, whereas FDR or both FDR and SDM were detected in the STM hybrids. All seven pairs of M chromosomes of Ae. comosa and C chromosomes of Ae. markgrafii were distinguished by fluorescent in situ hybridization (FISH) probes pSc119.2 and pTa71 combinations with pTa-535 and (CTT)12/(ACT)7, respectively. Meanwhile, the chromosomes of tetraploid wheat and diploid Aegilops parents were distinguished by the same FISH probes. The amphidiploids possessed specific valuable traits such as multiple tillers, large seed size related traits, and stripe rust resistance that could be utilized in the genetic improvement of wheat.

Recombination between G2 and G6 strains of rabbit hemorrhagic disease virus (RHDV) in China.

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the lagovirus rabbit hemorrhagic disease virus (RHDV), which was first reported in 1984 in China. Genetic characterization of RHDV has demonstrated that two different genogroups (G2 and G6) are present in China. To gain a better understanding of the molecular evolution of RHDV, we searched for recombination events by analyzing all full-length RHDV capsid VP60 sequences of Chinese isolates belonging to the genogroups 2 and 6. Our results revealed a recombinant origin for the NanBu/China/2011 isolate. This recombination event occurred between G2 and G6 strains with two breakpoints located at nucleotide positions 393 and 1079 of the VP60 sequence. Phylogenetically, the NanBu/China/2011 strain clustered with genogroup G6 in the entire capsid gene sequence except in the fragment between nucleotides 394 and 1078, where it clustered with genogroup G2. As the consequences of the presence of a G2/G6 recombinant strain in China are unpredictable, the circulation of RHDV in the populations should be carefully monitored.

Binding of rabbit hemorrhagic disease virus-like particles to host histo-blood group antigens is blocked by antisera from experimentally vaccinated rabbits.

During infection host histo-blood group antigens (HBGAs) act as attachment factors that interact with rabbit hemorrhagic disease virus (RHDV) and participate in the infectious process. In the present study, baculovirus expressing recombinant RHDV capsid protein (VP60r) as a vaccine immunogen was used to test its antigenicity and immunogenicity via immunization experiments. Each group of rabbits immunized with VP60r was found to be fully protected against RHDV challenge. The duration of immunity of the vaccine following the inoculation of a single dose was determined to be at least 240 days. RHDV-specific humoral responses in antisera from inoculated rabbits were analyzed using VP60r virus-like particle (VLP)-based ELISA. Anti-VP60-specific antibody was produced by 7 days post-primary immunization. Following this stage, the levels of this antibody increased steadily, peaking at 90 days and maintaining a high level until 240 days. We developed a synthetic carbohydrate assay to detect blockage in attachment of RHDV VLPs to HBGAs by the rabbit antisera. On day 7 post-immunization, serum samples were demonstrated to block the binding of H type 2 to RHDV VLPs, with a blocking rate of almost 60%, a value that then increased steadily over time. From day 60 to day 240 post-immunization, serum samples completely blocked the binding of H type 2 to RHDV VLPs, with a blocking rate of almost 100%. This indicated that VP60-induced antibodies neutralize the interaction of RHDV with HBGAs.

Thoughts on the research of African swine fever live-attenuated vaccines.

African swine fever (ASF) is a contagious and fatal disease caused by the African swine fever virus (ASFV), which can infect pigs of all breeds and ages. Most infected pigs have poor prognosis, leading to substantial economic losses for the global pig industry. Therefore, it is imperative to develop a safe and efficient commercial vaccine against ASF. The development of ASF vaccine can be traced back to 1960. However, because of its large genome, numerous encoded proteins, and complex virus particle structure, currently, no effective commercial vaccine is available. Several strategies have been applied in vaccine design, some of which are potential candidates for vaccine development. This review provides a comprehensive analysis on the safety and effectiveness, suboptimal immunization effects at high doses, absence of standardized evaluation criteria, notable variations among strains of the same genotype, and the substantial impact of animal health on the protective efficacy against viral challenge. All the information will be helpful to the ASF vaccine development.

Pien Tze Huang (PZH) protects endothelial function in diabetic mice.

Endothelial dysfunction is the most common pathological feature of cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. It affects both macro- and micro-vasculatures, causing functional impairment of multiple organs. Pien Tze Huang (PZH) is a well-studied traditional Chinese medicine (TCM) with multiple pharmacological properties that produces therapeutic benefits against colorectal cancer, non-alcoholic steatohepatitis and neurodegenerative diseases. However, it is unknown how PZH affects vascular function under pathological conditions. Therefore, this study aimed to investigate the effect of PZH on endothelial function and the underlying mechanisms in db/db diabetic mice. The results showed that chronic treatment of PZH (250 mg/kg/day, 5 weeks) improved endothelial function by restoring endothelium-dependent relaxation through the activation of the Akt-eNOS pathway and inhibition of endothelial oxidative stress, which increased nitric oxide bioavailability. Furthermore, PZH treatment increased insulin sensitivity and suppressed inflammation in diabetic mice. These new findings suggest that PZH may have vaso-protective properties and the potential to protect against diabetic vasculopathy by preserving endothelial function.

Myocardium-targeted liposomal delivery of the antioxidant peptide 8P against doxorubicin-induced myocardial injury.

Doxorubicin (Dox) is a broad-spectrum antineoplastic chemotherapeutic agent used in clinical settings, yet it exhibits significant cardiotoxicity, which in severe cases can lead to heart failure. Research indicates that oxidative stress plays a pivotal role in Dox -induced cardiomyocyte injury. Therefore, the application of antioxidants represents an effective strategy to mitigate the cardiotoxic effects of doxorubicin. In preliminary studies, we isolated an antioxidative peptide, PHWWEYRR (8P). This study utilizes a PCM cardiomyocyte-targeting peptide-modified liposome as a carrier to deliver 8P into cardiomyocytes, aiming to prevent Dox-induced cardiac injury through its antioxidative mechanism. The results demonstrated that we prepared the 8P-loaded and PCM-targeting peptide-modified liposome (P-P-8P), which exhibited good dispersibility, encapsulation efficiency, drug loading capacity, and in vitro release, along with myocardial targeting capability. In vitro experiments showed that P-P-8P could prevent oxidative stress injury in H9C2 cells, protect mitochondrial functions, and inhibit cell apoptosis through a mitochondria-dependent pathway. In vivo experiments indicated that P-P-8P could prevent abnormalities in serum biochemical indicators, cardiac dysfunction, and myocardial pathological changes in mice. In conclusion, P-P-8P effectively delivers 8P to cardiomyocytes, offering protection against the cardiotoxic effects of Dox, and holds potential as a future preventative or therapeutic agent for drug-induced cardiomyopathy.

Sesamin extends the mean lifespan of fruit flies.

The present study investigated the anti-ageing activity of sesamin and its effect on gene expression of superoxide dismutase (SOD), catalase (CAT), methuselah (Mth) and Rpn11 in Drosophila melanogaster. Results demonstrated that 0.2 % sesamin in diet prolonged the mean lifespan of OR wild fruit flies by 12 %, accompanied by up-regulation of SOD1, SOD2, CAT and Rpn11. Sesamin at 0.2 % in diet also attenuated paraquat-induced neurodegeneration with up-regulation of SOD1, SOD2 and Rpn11 in OR wild fruit flies. Supplementation of 0.2 % sesamin in diet increased the survival time of OR wild type flies and Alzheimer flies Aß42 33769 when they were challenged with paraquat. Furthermore, sesamin-induced increase in the activity and expression of antioxidant enzymes also suggests that the longevity promoting activity of sesamin are possibly due to its action as a hormetin by inducing oxidative stress response-mediated hormesis. It was concluded that sesamin extended the mean lifespan and alleviated the neurodegeneration in Drosophila melanogaster at least mediated by its interaction with genes SOD1, SOD2, CAT, and Rpn11, but not with gene Mth.

Blueberry anthocyanins at doses of 0.5 and 1 % lowered plasma cholesterol by increasing fecal excretion of acidic and neutral sterols in hamsters fed a cholesterol-enriched diet.

PURPOSE: The present study investigated the underlying mechanism associated with the hypocholesterolemic activity of blueberry anthocyanins by examining its effect on fecal sterol excretion and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism. METHODS: Hamsters were divided into three groups and fed a 0.1 % cholesterol diet containing 0 % (CTL), 0.5 % (BL), and 1.0 % (BH) blueberry anthocyanins, respectively, for six weeks. Plasma total cholesterol (TC), triacylglycerols (TAG), and non-high-density lipoproteins cholesterol (non-HDL-C) were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. GC analysis was used to quantify hepatic cholesterol and fecal acidic and neutral sterols. RESULTS: Dietary supplementation of 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12 % in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 22-29 % and 41-74 %, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of NPC1L1, ACAT-2, MTP, and ABCG 8. In addition, blueberry anthocyanins were also able to down-regulate the gene expression of hepatic HMG-CoA reductase. CONCLUSION: The cholesterol-lowering activity of blueberry anthocyanins was most likely mediated by enhancing the excretion of sterols accompanied with down-regulation on gene expression of intestinal NPC1L1, ACAT-2, MTP, and ABCG 8.

Capsaicinoids lower plasma cholesterol and improve endothelial function in hamsters.

PURPOSE: Capsaicinoids are the active compounds in chili pepper. The present study investigated the effect of capsaicinoids on plasma lipids, functionality of aorta including atherosclerotic plaque development, cholesterol absorption biomarker, fecal sterol excretion, and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism. METHODS: Hamsters were divided into five groups and fed a high-cholesterol diet containing 0 % (CON), 0.010 % (LD), 0.015 % (MD), 0.020 % (HD), and 0.030 % (VD) capsaicinoids, respectively, for 6 weeks. Plasma lipids were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. Endothelial function was assessed by measuring the acetylcholine-induced endothelium-dependent relaxations in aorta. RESULTS: Capsaicinoids reduced plasma total cholesterol, non-high-density lipoprotein cholesterol, and triacylglycerols with high-density lipoprotein cholesterol being unaffected. All four experimental groups had a decrease in the atherosclerotic plaque compared with CON. Dietary capsaicinoids increased the fecal excretion of total acidic sterols possibly mediated by up-regulation of cholesterol 7α-hydroxylase and down-regulation of liver X receptor alpha. Plasma sterol analysis demonstrated that capsaicinoids decreased the ratio of plasma campesterol/cholesterol, suggesting they decreased cholesterol absorption. Capsaicinoids could improve the endothelium-dependent relaxations and reduce the endothelium-dependent contractions by inhibiting the gene expression of COX-2. However, no dose-dependent effect of capsaicinoids on these parameters was seen. CONCLUSION: Capsaicinoids were beneficial in improving lipoprotein profile and aortic function in hamsters fed a high-cholesterol diet.